1.
Carl Ferdinand Cori
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In 2004 both were designated a National Historic Chemical Landmark in recognition of their work that elucidated carbohydrate metabolism. Carl was the son of Carl Isidor Cori, a zoologist, and Maria née Lippich, the Cori Family came from the Papal State to the Royal Bohemian Crownland, Austrian Circle at the end of the 17th century. Carl Ferdinands grandfather Eduard Cori was an officer and beekeeper in Brüx. Carl Ferdinands younger sister Margarete Cori was a lecturer of Prague and he grew up in Trieste, where his father Carl Isidor was the director of the Marine Biological Station. In late 1914 the Cori family moved to Prague and Carl entered the school of Charles University in Prague. While studying there he met Gerty Theresa Radnitz and he was drafted into the Austro-Hungarian Army and served in the ski corps, and later was transferred to the sanitary corps, for which he set up a laboratory in Trieste. At the end of the war Carl completed his studies, graduating with Gerty in 1920, Carl and Gerty married that year and worked together in clinics in Vienna. Carl was invited to Graz to work with Otto Loewi to study the effect of the vagus nerve on the heart, while Carl was in Graz, Gerty remained in Vienna. A year later Carl was offered a position at the State Institute for the Study of Malignant Diseases in Buffalo, New York, in 1928, they became naturalized citizens of the United States. While at the Institute the Coris’ research focused on carbohydrate metabolism, in 1931 Carl accepted a position at the Washington University School of Medicine in St. Louis, Missouri. Carl joined as professor of pharmacology and in 1942 was made professor of biochemistry, in St. Louis, the Coris continued their research on glycogen and glucose and began to describe glycogenolysis, identifying and synthesizing the important enzyme glycogen phosphorylase. For these discoveries, they received the Nobel Prize in Physiology or Medicine in 1947, Gerty died in 1957 and Carl married Anne Fitz-Gerald Jones in 1960. He stayed on at Washington University until 1966, when he retired as chair of the biochemistry department and he was appointed visiting professor of Biological Chemistry at Harvard University while maintaining a laboratory space at the Massachusetts General Hospital, where he pursued research in genetics. From 1968 to 1983 he collaborated with noted geneticist Salomé Glüecksohn-Waelsch of the Albert Einstein College of Medicine in New York, in 1976 Carl received the Laurea honoris causa in Medicine from the University of Trieste. Cori was elected a Foreign Member of the Royal Society in 1950 and the Carl Cori Endowed Professorship at Washington University is named in his honor, currently held by Colin Nichols
2.
Gerty Cori
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Gerty was not a nickname, but rather she was named after an Austrian warship. Because of deteriorating conditions in Europe, the couple emigrated to the United States in 1922, Gerty Cori continued her early interest in medical research, collaborating in the laboratory with Carl. She published research findings coauthored with her husband, as well as publishing singly, unlike her husband, she had difficulty securing research positions, and the ones she obtained provided meager pay. Her husband insisted on continuing their collaboration, though he was discouraged from doing so by the institutions that employed him and they also identified the important catalyzing compound, the Cori ester. In 2004, both Gerty and Carl Cori were designated a National Historic Chemical Landmark in recognition of their work in clarifying carbohydrate metabolism, in 1957, Gerty Cori died after a ten-year struggle with myelosclerosis. She remained active in the laboratory until the end. She received recognition for her achievements through multiple awards and honors, the Cori crater on the Moon and the Cori crater on Venus are named after her. Gerty Theresa Radnitz was born into a Jewish family in Prague in 1896 and her father, Otto Radnitz, was a chemist who became manager of sugar refineries after inventing a successful method for refining sugar. Her mother, Martha, a friend of Franz Kafka, was a sophisticated woman. Gerty was tutored at home before enrolling in a Lyceum for girls, pursuing the study of science, Gerty learned that she lacked the prerequisites in Latin, physics, chemistry, and mathematics. Over the course of a year, she managed to study the equivalent of eight years of Latin, five years of science and her uncle, a professor of pediatrics, encouraged her to attend medical school, so she studied for and passed the University entrance examination. She was admitted to the school of the Karl-Ferdinands-Universität in Prague in 1914. While studying she met Carl Cori who was attracted to her charm, vitality, sense of humor and her love of the outdoors. Gerty and Carl had both entered medical school at eighteen and both graduated in 1920, Gerty converted to Catholicism, enabling her and Carl to marry in the Roman Catholic Church. They moved to Vienna, Austria, where Gerty spent the two years at the Carolinen Childrens Hospital, and her husband worked in a laboratory. Carl served in the Austrian army during World War I after being drafted, life was difficult following World War I, and Gerty suffered from xerophthalmia caused by severe malnutrition due to food shortages. These problems, in conjunction with the increasing anti-Semitism, contributed to the Coris decision to leave Europe, in 1922, the Coris both immigrated to the United States to pursue medical research at the State Institute for the Study of Malignant Diseases in Buffalo, New York. In 1928, they became naturalized citizens of the United States, the director for the Institute threatened to dismiss Gerty if she did not cease collaborative research with her husband
3.
Lactic acid
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Lactic acid is an organic compound with the formula CH3CHCO2H. In its solid state, it is white and water-soluble, in its liquid state, it is clear. It is produced naturally and synthetically. With a hydroxyl group adjacent to the group, lactic acid is classified as an alpha-hydroxy acid. In the form of its base called lactate, it plays a role in several biochemical processes. In solution, it can ionize a proton from the carboxyl group, compared to acetic acid, its pKa is 1 unit less, meaning lactic acid deprotonates ten times more easily than acetic acid does. This higher acidity is the consequence of the hydrogen bonding between the α-hydroxyl and the carboxylate group. Lactic acid is chiral, consisting of two optical isomers, one is known as L--lactic acid or -lactic acid and the other, its mirror image, is D--lactic acid or -lactic acid. A mixture of the two in equal amounts is called DL-lactic acid, or racemic lactic acid, DL-lactic acid is miscible with water and with ethanol above its melting point which is around 17 or 18 °C. D-lactic acid and L-lactic acid have a melting point. In animals, L-lactate is constantly produced from pyruvate via the enzyme lactate dehydrogenase in a process of fermentation during normal metabolism and exercise. The concentration of lactate is usually 1–2 mmol/L at rest. In industry, lactic acid fermentation is performed by lactic acid bacteria and these bacteria can also grow in the mouth, the acid they produce is responsible for the tooth decay known as caries. In medicine, lactate is one of the components of lactated Ringers solution. These intravenous fluids consist of sodium and potassium cations along with lactate and chloride anions in solution with distilled water and it is most commonly used for fluid resuscitation after blood loss due to trauma, surgery, or burns. Lactic acid was isolated for the first time by the Swedish chemist Carl Wilhelm Scheele in 1780 from sour milk, the name reflects the lact- combining form derived from the Latin word for milk. In 1808, Jöns Jacob Berzelius discovered that lactic acid also is produced in muscles during exertion and its structure was established by Johannes Wislicenus in 1873. In 1856, Louis Pasteur discovered Lactobacillus and its role in the making of lactic acid, lactic acid started to be produced commercially by the German pharmacy Boehringer Ingelheim in 1895
4.
Glycolysis
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Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+. The free energy released in this process is used to form the high-energy molecules ATP, glycolysis is a determined sequence of ten enzyme-catalyzed reactions. The intermediates provide entry points to glycolysis, for example, most monosaccharides, such as fructose and galactose, can be converted to one of these intermediates. The intermediates may also be directly useful, for example, the intermediate dihydroxyacetone phosphate is a source of the glycerol that combines with fatty acids to form fat. Glycolysis is an oxygen independent metabolic pathway, meaning that it not use molecular oxygen for any of its reactions. However the products of glycolysis are sometimes metabolized using atmospheric oxygen, when molecular oxygen is used for the metabolism of the products of glycolysis the process is usually referred to as aerobic, whereas if no oxygen is used the process is said to be anaerobic. Thus, glycolysis occurs, with variations, in all organisms. The wide occurrence of glycolysis indicates that it is one of the most ancient metabolic pathways, glycolysis could thus have originated from chemical constraints of the prebiotic world. Glycolysis occurs in most organisms in the cytosol of the cell, the most common type of glycolysis is the Embden–Meyerhof–Parnas, which was discovered by Gustav Embden, Otto Meyerhof, and Jakub Karol Parnas. Glycolysis also refers to other pathways, such as the Entner–Doudoroff pathway, however, the discussion here will be limited to the Embden–Meyerhof–Parnas pathway. The overall reaction of glycolysis is, The use of symbols in this equation makes it appear unbalanced with respect to oxygen atoms, hydrogen atoms, and charges. In the cellular environment, all three groups of ADP dissociate into −O− and H+, giving ADP3−, and this ion tends to exist in an ionic bond with Mg2+. ATP behaves identically except that it has four groups, giving ATPMg2−. When these differences along with the charges on the two phosphate groups are considered together, the net charges of −4 on each side are balanced. For simple fermentations, the metabolism of one molecule of glucose to two molecules of pyruvate has a net yield of two molecules of ATP, most cells will then carry out further reactions to repay the used NAD+ and produce a final product of ethanol or lactic acid. Many bacteria use inorganic compounds as hydrogen acceptors to regenerate the NAD+, cells performing aerobic respiration synthesize much more ATP, but not as part of glycolysis. These further aerobic reactions use pyruvate and NADH + H+ from glycolysis, the pathway of glycolysis as it is known today took almost 100 years to fully discover. The combined results of many experiments were required in order to understand the pathway as a whole
5.
Nobel Prize in Physiology or Medicine
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The Nobel Prize in Physiology or Medicine, administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the fields of life sciences and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, Nobel was personally interested in experimental physiology and wanted to establish a prize for progress through scientific discoveries in laboratories. The Nobel Prize is presented to the recipient at a ceremony on 10 December, the anniversary of Nobels death, along with a diploma. The front side of the medal provides the profile of Alfred Nobel as depicted on the medals for Physics, Chemistry. As of 2015,106 Nobel Prizes in Physiology or Medicine have been awarded to 198 men and 12 women. The first Nobel Prize in Physiology or Medicine was awarded in 1901 to the German physiologist Emil von Behring, for his work on serum therapy and this includes one to António Egas Moniz in 1949 for the prefrontal leucotomy, bestowed despite protests from the medical establishment. Other controversies resulted from disagreements over who was included in the award, the 1952 prize to Selman Waksman was litigated in court, and half the patent rights awarded to his co-discoverer Albert Schatz who was not recognized by the prize. The 1962 prize awarded to James D, since the Nobel Prize rules forbid nominations of the deceased, longevity is an asset, one prize being awarded as long as 50 years after the discovery. Alfred Nobel was born on 21 October 1833 in Stockholm, Sweden into a family of engineers and he was a chemist, engineer and inventor who amassed a fortune during his lifetime, most of it from his 355 inventions of which dynamite is the most famous. He was interested in experimental physiology and set up his own labs in France, in 1888, Nobel was surprised to read his own obituary, titled The merchant of death is dead, in a French newspaper. Though Nobel wrote several wills during his lifetime, the last was written a little over a year before he died at the age of 63, because his will was contested, it was not approved by the Storting until 26 April 1897. After Nobels death, the Nobel Foundation was set up to manage the assets of the bequest, in 1900, the Nobel Foundations newly created statutes were promulgated by Swedish King Oscar II. According to Nobels will, the Karolinska Institutet in Sweden, a medical school, today, the prize is commonly referred to as the Nobel Prize in Medicine. It was important to Nobel that the prize be awarded for a discovery, per the provisions of the will, only select persons are eligible to nominate individuals for the award. Past Nobel laureates may also nominate, until 1977, all professors of Karolinska Institutet together decided on the Nobel Prize in Physiology or Medicine. Therefore, the Nobel Assembly was constituted, consisting of 50 professors at Karolinska Institutet. It elects the Nobel Committee with 5 members who evaluate the nominees, the Secretary who is in charge of the organization, in 1968, a provision was added that no more than three persons may share a Nobel prize. True to its mandate, the Committee has selected researchers working in the sciences over those who have made applied contributions
6.
Adenosine triphosphate
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Adenosine triphosphate is a nucleotide, also called a nucleoside triphosphate, is a small molecule used in cells as a coenzyme. It is often referred to as the unit of currency of intracellular energy transfer. ATP transports chemical energy within cells for metabolism, most cellular functions need energy in order to be carried out, synthesis of proteins, synthesis of membranes, movement of the cell, cellular division, transport of various solutes etc. The ATP is the molecule that carries energy to the place where the energy is needed, when ATP breaks into ADP and Pi, the breakdown of the last covalent link of phosphate liberates energy that is used in reactions where it is needed. Substrate-level phosphorylation, oxidative phosphorylation in cellular respiration, and photophosphorylation in photosynthesis are three mechanisms of ATP biosynthesis. Metabolic processes that use ATP as an energy source convert it back into its precursors, ATP is therefore continuously recycled in organisms, the human body, which on average contains only 250 grams of ATP, turns over its own body weight equivalent in ATP each day. ATP is used as a substrate in signal transduction pathways by kinases that phosphorylate proteins and it is also used by adenylate cyclase, which uses ATP to produce the second messenger molecule cyclic AMP. The ratio between ATP and AMP is used as a way for a cell to sense how much energy is available and control the metabolic pathways that produce and consume ATP. Apart from its roles in signaling and energy metabolism, ATP is also incorporated into nucleic acids by polymerases in the process of transcription, ATP is the neurotransmitter believed to signal the sense of taste. The structure of this consists of a purine base attached by the 9′ nitrogen atom to the 1′ carbon atom of a pentose sugar. Three phosphate groups are attached at the 5′ carbon atom of the pentose sugar and it is the addition and removal of these phosphate groups that inter-convert ATP, ADP and AMP. When ATP is used in DNA synthesis, the sugar is first converted to deoxyribose by ribonucleotide reductase. ATP was discovered in 1929 by Karl Lohmann, and independently by Cyrus Fiske and Yellapragada Subbarow of Harvard Medical School and it was proposed to be the intermediary molecule between energy-yielding and energy-requiring reactions in cells by Fritz Albert Lipmann in 1941. It was first artificially synthesized by Alexander Todd in 1948, ATP consists of adenosine – composed of an adenine ring and a ribose sugar – and three phosphate groups. The phosphoryl groups, starting with the group closest to the ribose, are referred to as the alpha, beta, consequently, it is closely related to the adenosine nucleotide, a monomer of RNA. ATP is highly soluble in water and is stable in solutions between pH6.8 and 7.4, but is rapidly hydrolysed at extreme pH. Consequently, ATP is best stored as an anhydrous salt, ATP is an unstable molecule in unbuffered water, in which it hydrolyses to ADP and phosphate. This is because the strength of the bonds between the groups in ATP is less than the strength of the hydrogen bonds, between its products, and water
7.
Glycogen
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Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in humans, animals, and fungi. The polysaccharide structure represents the main form of glucose in the body. In humans, glycogen is made and stored primarily in the cells of the liver, glycogen functions as the secondary long-term energy storage, with the primary energy stores being fats held in adipose tissue. Muscle glycogen is converted into glucose by muscle cells, and liver glycogen converts to glucose for use throughout the body including the nervous system. Glycogen is the analogue of starch, a polymer that functions as energy storage in plants. It has a similar to amylopectin, but is more extensively branched. Both are white powders in their dry state, glycogen is found in the form of granules in the cytosol/cytoplasm in many cell types, and plays an important role in the glucose cycle. Glycogen forms a reserve that can be quickly mobilized to meet a sudden need for glucose. In the liver, glycogen can make up from 5–6% of the fresh weight. Only the glycogen stored in the liver can be accessible to other organs. In the muscles, glycogen is found in a low concentration, the amount of glycogen stored in the body—especially within the muscles, liver, and red blood cells—mostly depends on physical training, basal metabolic rate, and eating habits. Small amounts of glycogen are found in the kidneys, and even smaller amounts in certain cells in the brain. The uterus also stores glycogen during pregnancy to nourish the embryo, glycogen is a branched biopolymer consisting of linear chains of glucose residues with further chains branching off every 8 to 12 glucoses or so. Glucoses are linked together linearly by α glycosidic bonds from one glucose to the next, branches are linked to the chains from which they are branching off by α glycosidic bonds between the first glucose of the new branch and a glucose on the stem chain. Due to the way glycogen is synthesised, every glycogen granule has at its core a glycogenin protein. Glycogen in muscle, liver, and fat cells is stored in a hydrated form, as a meal containing carbohydrates or protein is eaten and digested, blood glucose levels rise, and the pancreas secretes insulin. Blood glucose from the vein enters liver cells. Insulin acts on the hepatocytes to stimulate the action of several enzymes, glucose molecules are added to the chains of glycogen as long as both insulin and glucose remain plentiful
8.
Skeletal muscle
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Skeletal muscle is one of three major muscle types, the others being cardiac muscle and smooth muscle. It is a form of striated muscle tissue which is under the control of the somatic nervous system. Most skeletal muscles are attached to bones by bundles of collagen fibers known as tendons, a skeletal muscle refers to multiple bundles of cells called muscle fibers. The fibres and muscles are surrounded by connective tissue layers called fasciae, Muscle fibres, or muscle cells, are formed from the fusion of developmental myoblasts in a process known as myogenesis. Muscle fibres are cylindrical, and have more than one nucleus, Muscle fibers are in turn composed of myofibrils. The myofibrils are composed of actin and myosin filaments, repeated in units called sarcomeres, the sarcomere is responsible for the striated appearance of skeletal muscle, and forms the basic machinery necessary for muscle contraction. Connective tissue is present in all muscles as fascia, Muscle fibres are the individual contractile units within muscle. A single muscle such as the biceps contains many muscle fibres, another group of cells, the myosatellite cells are found between the basement membrane and the sarcolemma of muscle fibers. These cells are normally quiescent but can be activated by exercise or pathology to provide additional myonuclei for muscle growth or repair, development Individual muscle fibers are formed during development from the fusion of several undifferentiated immature cells known as myoblasts into long, cylindrical, multi-nucleated cells. Differentiation into this state is completed before birth with the cells continuing to grow in size thereafter. Microanatomy Skeletal muscle exhibits a distinctive banding pattern when viewed under the due to the arrangement of cytoskeletal elements in the cytoplasm of the muscle fibers. The principal cytoplasmic proteins are myosin and actin which are arranged in a unit called a sarcomere. The interaction of myosin and actin is responsible for muscle contraction, every single organelle and macromolecule of a muscle fiber is arranged to ensure form meets function. The cell membrane is called the sarcolemma with the known as the sarcoplasm. In the sarcoplasm are the myofibrils, the myofibrils are long protein bundles about 1 micrometer in diameter each containing myofilaments. Pressed against the inside of the sarcolemma are the unusual flattened myonuclei, between the myofibrils are the mitochondria. While the muscle fiber does not have a smooth endoplasmic reticulum, the sarcoplasmic reticulum surrounds the myofibrils and holds a reserve of the calcium ions needed to cause a muscle contraction. Periodically, it has dilated end sacs known as terminal cisternae and these cross the muscle fiber from one side to the other
9.
Glycogenolysis
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Glycogenolysis is the breakdown of glycogen to glucose-6-phosphate and glycogen. Glycogen branches are catabolized by the removal of glucose monomers via phosphorolysis. Glucose-1-phosphate is converted to glucose-6-phosphate by the enzyme phosphoglucomutase, glucose residues are phosphorolysed from branches of glycogen until four residues before a glucose that is branched with a α linkage. Glycogen debranching enzyme then transfers three of the remaining four units to the end of another glycogen branch. This exposes the α branching point, which is hydrolysed by α glucosidase, removing the final glucose residue of the branch as a molecule of glucose and this is the only case in which a glycogen metabolite is not glucose-1-phosphate. The glucose is subsequently phosphorylated to glucose-6-phosphate by hexokinase, Glycogenolysis takes place in the cells of the muscle and liver tissues in response to hormonal and neural signals. In particular, glycogenolysis plays an important role in the fight-or-flight response, in myocytes, glycogen degradation serves to provide an immediate source of glucose-6-phosphate for glycolysis, to provide energy for muscle contraction. In hepatocytes, the purpose of the breakdown of glycogen is for the release of glucose into the bloodstream for uptake by other cells. Glycogenolysis is regulated hormonally in response to blood sugar levels by glucagon and insulin, in myocytes, glycogen degradation may also be stimulated by neural signals. Parenteral administration of glucagon is a human medical intervention in diabetic emergencies when sugar cannot be given orally. It can also be administered intramuscularly, mutations at the liver enzyme glycogen phosphorylase lead to glycogen storage disease VI. Mutations at the enzyme glycogen phosphorylase lead to McArdles disease. Deficiencies at the glycogen debranching enzyme lead to glycogen storage disease III, glycogenesis The chemical logic of glycogen degradation at ufp. pt Glycogenolysis at the US National Library of Medicine Medical Subject Headings
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